Optically enriched alkyl(2S,3R)-phenylglycidate and alkyl(2R,3S)-phenyl-glycidate of formulae 7 and 8 are the key intermediates used in the synthesis of N-benzoyl-(2R,3S)-3-phenylisoserine (Taxol side chain). Paclitaxel or Taxol which was isolated from the bark of the Pacific Yew (Taxus brevifolia)(Wani et al J Am Chem Soc. 93, 2325–7 1971) and has been approved for the treatment of
various types of cancers(Holmes et al J. Natl. Cancer Inst. 83, 1797–1805,1991).
Despite being one of the most promising anti-cancer drugs, its very low occurrence (40–165 mg/kg) in nature is the main hindrance in its production. Fortunately it has been found that 10-deacetyl baccatin-III which is structurally closely related to Taxol and occurs in comparatively higher concentrations (approx. 1 g/kg), can be easily isolated from fresh leaves of European Yew (Taxus baccata). It is also reported that Paclitaxel is 1000 times more potent compared to 10-deacetyl baccatin-III and its higher activity is due to a C-13 side chain comprising N-benzoyl-(2R,3S)-3-phenylisoserine moiety (Wani et al J Am Chem Soc. 93, 2325–7 1971).

Therefore synthesis of optically active (2S,3R) and (2R,3S)-phenylglycidates of formula 7 and 8 which are the key chiral precursors for synthesising N-benzoyl-(2R,3S)-3-phenylisoserine has become very vital for the development of a practical and efficient route to synthesise enantiomerically pure isoserine chain.
There are number of reports on the preparation of these chiral intermediates by biochemical or chemoenzymatic methods besides asymmetric syntheses. Most of these reports are related to kinetic resolution of racemic 2-halo-3-hydroxy-3-phenylpropanoate through enzymatic hydrolysis (H. Honig et al., Tetrahedron 46, 3841–3850, 1990; Peter G. M Wuts et al, Tetrahedron Asymmetry 11, 2117–2123, 2000), or by transesterification reaction (Ching-Shih Chen et al., J. Org. Chem. 58, 1287–1289, 1993; Ching-Shih Chen et al, U.S. Pat. No. 6,020,174, to The Board of Governors for Higher Education, Rhodes Island; Marco Villa et al., U.S. Pat. No. 6,187,936 to Zambon Group S.p.A; Tanebe JP 06/078790) or via resolution of azetidinones (C. J Sih et al., J. Org. Chem. 58, 1068–1075, 1993; R. N. Patel et al, J. American Oil Chemists Society, 73, 1363–1375, 1996; R. A. Holton et al, WO 2001029245, EP 1222305 to Bristol-Myers Squibb; R. N. Patel et al., Biotechnology and Applied Biochemistry, 20, 23–33, 1994).
From the literature review it is quite clear that no prior art is available on kinetic resolution of racemic 2-halo-3-hydroxy-3-phenylpropanoates where x represents bromo and iodo groups and R′ represents C-1 to C-5 alky group. Therefore the use of bromo and iodohydrins via kinetic resolution route for the preparation of desired (2S,3R) and (2R,3S)-phenylglycidates in essentially novel and has not been reported in the literature or known in the art of their synthesis of taxol side chain precursors.
The present invention therefore discloses the application of a lipase for the preparation of (2S,3R) and (2R,3S)-phenylglycidates via kinetic resolution of halohydrin intermediates x and R′ are defined as above.